CONVERSATION BETWEEN DR. RICCARDO BASCHETTI OF ITALY AND DAVID WILLIAMS CONCERNING TREATING CHRONIC FATIGUE SYNDROME WITH LICORICE EXTRACT

David Wms: Please tell me about your use of licorice in the treatment of CFS

Dr. Baschetti: Before describing my therapy, I must emphasize that it is effective only in the treatment of CHRONIC FATIGUE SYNDROME (CFS) and that it might be harmful in other, albeit similar conditions. Therefore, a correct diagnosis is absolutely essential before beginning my treatment with licorice. In particular, if you never had enlarged and painful lymph nodes, you do not have CFS. The symptoms of CFS are very similar to those of depression, but lymphadenopathy (disease of the lymph node), which is absent in depressed patients, is the major discriminating factor between the two conditions. Moreover, if your blood pressure tends to hypertension, you do not have CFS. An additional discriminating factor is cortisolemia; if your plasma cortisol levels are above normal values, you do not have CFS. Patients with CFS have low plasma cortisol levels; depressed patients, by contrast, have high plasma cortisol levels. Since licorice is effective in CFS mainly because it potentiates the action of cortisol, you must certainly realize that licorice can worsen depression. Further, since licorice retains sodium it is harmful to those whose blood pressure tends to hypertension.

 

David Wms: Are you saying that if your blood pressure tends towards hypertension, then you do not have Chronic Fatigue Syndrome?

 

Dr. Baschetti: Yes, if you have hypertension, and/or if you never had enlarged and painful lymph nodes, you do not have CFS.

 

David Wms: Then if you have high blood pressure, you should not take licorice?

 

Dr. Baschetti: Absolutely! No one with hypertension should be taking licorice. The herb is effective only in the treatment of CFS with neurally mediated hypotension. Licorice might be harmful in other, albeit similar conditions, therefore, a correct diagnosis is absolutely essential before beginning my therapy.

 

David Wms: What is your recommended dose of licorice?

 

Dr. Baschetti: Two grams of pure, non-deglycyrrhinized licorice must be completely dissolved in half a liter (500 ml) of cold whole milk. The beverage (milk plus licorice) must be drunk every morning as a unique breakfast. The beverage can be sugared with about 15-20 grams of sucrose or honey. If you have really CFS, which is an atypical adrenal insufficiency, you should considerably improve in a few hours. Nevertheless, if your improvement is poor, you can gradually and cautiously increase the dosage of licorice up to 5 grams in the usual half a liter of milk. Several months later, only if the improvement is still insufficient, to potentiate the effectiveness of the beverage, you can dissolve in it also 2.5 milligrams of hydrocortisone (a quarter of tablet).

 

David Wms: Why milk?

 

Dr. Baschetti: Your question concerning the use of milk is important, therefore I will answer and include scientific references to support my reasoning.

 

To fully explain why I recommend to dissolve licorice in milk, I must sum up briefly my personal experience with licorice. In October 1994, my 20th month with CFS, I started trying licorice. While lots of previously tried drugs had completely failed to improve my CFS symptoms, dry licorice relieved them significantly. To improve further, I increased the dosage of dry licorice up to 30 g/day. However, although feeling better, I was still far from my pre-morbid state. I therefore hypothesized that the beneficial sodium-retaining action of licorice could be potentiated by dissolving licorice in a liquid food rich in sodium. The liquid state of food, obviously, allows to obtain homogeneous distribution of licorice and, as a result, its gradual and simultaneous absorption along with sodium (1). I chose milk because I like it, I never had lactose intolerance, and mainly because milk has a constant, high content of sodium (about 510 mg/L; by contrast, in comparison, no fruit juice exceeds 30 mg/L of sodium).

 

My hypothesis proved correct. In fact, after taking licorice dissolved in milk, in a few hours I felt virtually recovered. Since then, 22 October 1994, the daily consumption of licorice dissolved in milk continues to keep me in excellent conditions. In the light of my personal successful experience, I recommend licorice dissolved in milk in the treatment of CFS. Those who have both CFS and lactose intolerance may obviously find my therapy problematic and may wish to take a lactase enzyme which should be readily available. Also, in view of the unexpectedly large subgroup of CFS patients and lactose intolerance who do not wish to take the enzyme, I now can suggest them some substitutes for milk.

 

Considering that, in my original protocol, milk works excellently thanks to its sodium content, I propose that milk can be replaced with isocaloric sugar solutions containing sodium concentrations similar to that of milk. Isostar (2), a widely used sport drink, contains about the same sodium concentration of milk (552 mg/l vs 50 mg/L). Gatorade, another famous sport drink, contains 483 mg/L of sodium (2). Those drinks, therefore, having sodium concentrations similar to that of milk, might replace it in my protocol. Such drinks, however, are by far less caloric than whole milk. The latter provides about 620 kcal/L, while Isostar and Gatorade provide 292 kcal/L and 240 kcal/L, respectively (2). Therefore, to approaching the caloric concentration of milk, Isostar and Gatorade must be sweetened with 82 g/L and 95g/L of sucrose, respectively. I recommend brown sugar, which, unlike white sugar, is rich in minerals. Given that 500 ml/day of sport drinks are sufficient, about 40-45 g of sucrose must be dissolved in the daily dose of those drinks.

 

One can ask why such drinks must be rendered more caloric. This is important because the caloric concentration of liquid foods determines the rate of gastric emptying (3-10) and, as a consequence, determines also the rate of absorption. Incidentally, in my view, it is the rate of absorption (regulated, in turn, by plasma glucose levels) that determines the rate of gastric emptying, not the reverse. This is another issue, however.

 

Extensive evidence (3-10) shows that the liquid foods, unlike the solid ones (11), empty linearly and more slowly with increasing volume and caloric concentration so that the delivery of solute to the small intestine is constant over time and across different caloric concentrations. However, when caloric concentration exceeds 1000kcal/L, gastric emptying does not slow further. As a result, with each increment in caloric concentration above 1000kcal/l, there is more rapid delivery of calories to the small bowel, i.e, a loss of regulation to caloric concentration (70).

 

David Wms: But 500 ml of milk seems like a lot. Why wouldn't a large cup full (250 ml) work just as well?

 

Dr. Baschetti: Given that, ideally, any hormonal replacement supplementation should obviously be absorbed gradually and slowly as to mimic the physiologic, endogenous hormonal production, it is better that licorice, which practically acts a simultaneous glucocorticoid and mineralocorticoid replacement supplementation (12), be dissolved in high-calorie solutions, which are absorbed far more slowly that low-calorie solutions. For this reason, I recommend to dissolve the daily dose of licorice in half a liter of whole milk. Only 250 ml of milk, besides being absorbed in half the time, provide an insufficient quantity of sodium, which, as discussed above, plays a central role in the treatment of CFS. In conclusion, my original therapy (licorice dissolved in milk) can be adapted to CFS patients with lactose intolerance by replacing milk with sugar solutions, as long as they have the same volume, caloric concentration, and sodium content of whole milk. One could object that sugar solutions provide calories only as carbohydrate, whereas whole milk provides calories as carbohydrate (lactose), protein, and fat. However, isocaloric concentrations of carbohydrate, protein, and fat produce equal slowing of gastric emptying (8). Of course, instead of using Isostar or Gatorade, one could prepare homemade sugar solutions. In this case, 500 ml of sugar solution must contain about 75 g/L of sucrose and about 650 mg of salt (sodium chloride), in which only 39% is sodium. However, to measure the very small quantity of salt, one should use a precision balance or laborious progressive dilutions. A wrong weighting of salt might result in homemade sugar solutions being either hypertensive or ineffective. By contrast, milk and sport drinks have constant sodium content.

 

Finally, I must stress that licorice can only help patients with real CFS. Those who do not have the physical signs and symptoms of the CDC diagnostic criteria (13) are unlikely to have CFS (14). In particular, those who have neither swollen lymph nodes (15) nor neurally mediated hypotension (16,17) are very unlikely to have CFS. Further, those who do not display hypocortisolemia, which characterizes CFS patients (18, 19), do not have the syndrome. As I pointed out in my first published report on licorice and CFS (20), licorice might worsen the symptoms of those who do not have real CFS.

 

David Wms: Will everyone with CFS have to take the same dose of licorice?

 

Dr. Baschetti: It has been consistently shown that CFS patients display both glucocorticoid and mineralocorticoid insufficiently, secondary to hypofunction of the hypothalamic-pituitary-adrenal axis. However, the degree of respective steroid insufficiency might be very different between patients. In other words, some patients might have very slight glucocorticoid (cortisol) insufficiency and, conversely, considerable mineralocorticoid insufficiency; some others (such as you perhaps) might have the opposite. This hypothesis might explain why the mineralocorticoid supplementation with Florinef was reportedly resolutive in about 50% of CFS patients but ineffective in the others. This hypothesis, although likely, can only be speculative because to date not published study dealt with the issue.

 

David Wms: How can I tell how much licorice to take?

 

Dr. Baschetti: I suggest you to go on empirically, by regulating the dosage on the basis of your physical conditions. This goal, in my view, can be more easily achieved with a precision balance, which will be even more useful when you will take the best grade licorice.

 

David Wms: How long will people with CFS need to take licorice?

 

Dr. Baschetti: Licorice used in CFS can only be a lifelong treatment. I started to take licorice dissolved in milk on 22 October 1994. Even though, since then, I never stopped taking licorice because the memory of my previous sufferings is dissuasive enough, there is indirect suggestion that withdrawal is harmful. In fact, to keep my restored good condition, I had to increase gradually the dosage of licorice. Initially, I used 2 grams per day, eventually going to 5 grams daily. But I am now down to needing only 4 grams per day.

 

Capt Wms: I disappointed that this treatment must be continued for the rest of my life.

 

Dr. Baschetti: Considering that CFS is an a typical adrenal insufficiency similar to classic Addison's disease, which unfortunately needs lifelong treatment, I think that, similarly, licorice within dissolved in milk will be our lifelong therapy. Be aware that within a few months, to keep your good conditions, you might need also small doses (2.5 mg/day) of hydrocortisone (to be added to milk+licorice).

 

Capt Wms: I added 3 mg of hydrocortisone to my licorice and became depressed within 3 days. What's going on here?

 

Dr. Baschetti: It is not surprising that you began to feel depressed after taking hydrocortisone. As I wrote in my fax of 28 April, you might need hydrocortisone "within a few months", not now. Your hypocortisolemia lasted 20 years. As a consequence, your glucocorticoid receptors (GR) have an enhanced sensitivity. This explains why for some months even small doses of hydrocortisone added to licorice, which greatly potentiates its action, may result in effects similar to those produced by hypercortisolemia, a typical abnormality of depressed subjects. Hydrocortisone, therefore, should only be taken some months later, when the sensitivity of your GR will be gradually normalized. Of course, the hypersensitivity of GR may well explain why licorice, initially, is extremely effective even at very small doses. The gradual normalization of the GR's sensitivity leads to the requirement of parallel increased dosage of licorice. I must stress, however, that your future use of hydrocortisone, although probable, is not mandatory. In other words, if licorice dissolved in milk will continue to be sufficient to keep good conditions, the drug will not be necessary.

 

David Wms: You recommended not taking potassium and I understood this to be because people with real CFS retained potassium and excreted salt, therefore supplementing potassium was wrong. It seems that many people are alarmed by not taking potassium with licorice. Should people who truly have CFS a concerned with potassium? I have had my potassium and other minerals monitored weekly and so far everything is normal.

 

Dr. Baschetti: Your explanation about not taking potassium supplements is correct. Indeed, as I pointed out in my fax of 4 March, potassium supplements, in CFS, are not only unnecessary, but even contraindicated. As it has been recently reported (1), even patients dying for undiagnosed Addison's disease may display serum potassium levels only slightly above normal range. Therefore, even though abnormally high serum potassium levels have not been reported in CFS patients, potassium supplements are certainly contraindicated in treating CFS, which is very similar to Addison's disease. Both conditions, in fact, cause swollen lymph nodes (2), asthenia, weakness, fever, fatiguability, arthralgia, myalgia (3), depression, confusion, inability to concentrate, forgetfulness, irritability, and disturbed sleep (3-5). Moreover, both CFS and Addison's disease predominantly affect females 30-50 old(3). Additionally, both conditions virtually resolve thanks to licorice (6-8) or greatly improve with fludro-cortisone (3,9-10).

 

David Wms: What I have read leads me to believe that CFS is caused by a virus. Do you agree? If so, would not the anti-viral effect of licorice be an added benefit, and maybe lead to a complete cure?

 

Dr. Baschetti: I agree that the cause of CFS is viral. In fact, most CFS patients report abrupt onset of "flu-like" symptoms. However, considering that thus far no single causative virus has been found in CFS patients, I believe that some virus does trigger CFS, by damaging irreparably the hypothalamic-pituitary-adrenal (HPA) axis, but within a few days it goes away. Once damaged, the HPA axis causes both hypocortisolism and mineralocorticoid insufficiency, which accounts for all the physical and the neuropsychological complaints of CFS. Given that no particular virus lives in CFS patients, the anti-viral effects of licorice are useless in those patients, who, however, improve with licorice thanks to its cortisol-potentiating and sodium-retaining effects.

 

David Wms: I believe that what Dr. Simpson is saying about damaged red blood cells might have a lot to do with the reduced adrenal gland function. Could your theory and his be interconnected?

 

Dr. Baschetti: I have read most of Dr. Simpson's papers, and, as you have correctly felt, Dr. Simpson's hypothesis and mine are somehow interconnected. However, while I cannot exclude that nondiscocytes may play a role in CFS, nonetheless I firmly believe that their increased size in CFS is an additional mere consequence (as are NMH, hypoperfusion, immunological abnormalities, and so on) of the atypical adrenal insufficiency that underlies CFS. In fact, after correcting both my hypocortisolism and my mineralocorticoid insufficiency with licorice dissolved in milk, I virtually recovered from CFS in only two hours.